Inflammatory cell recruitment and cytokine production in a rat model of acute silicosis:modifying effects of endotoxin.

The recruitment of inflammatory cells into the lungs of PVG rats was studied following intratracheal instillation of phosphate-buffered saline (PBS) or various doses (1,0.1 and 0.01 mg) of DQ12 quartz and titanium dioxide (TiO2) suspended in PBS. Tumour necrosis factor (TNF) activity was measured in the supernatants of cultures of lavaged cells. In contrast to animals receiving PBS, TiO2 or 0.01 mg quartz where initial inflammatory responses had mostly resolved by day 7, neutrophil and macrophage numbers remained greatly elevated at day 21 in animals treated with 1 mg quartz and above normal levels in those receiving 0.1 mg. The addition of 80 μg LPS to the 0.01 mg quartz inoculum caused a synergistic inflammatory response at day 1 which resolved by day 7. TNF activity peaked at day 3 for PBS and TiO2 and was still elevated at day 7 when inflammation had largely resolved. Cells from LPS- or quartz-treated animals gave their peak response at day 7 but activity was greatly reduced at day 21 despite continuing inflammation in the 0.1 and 1 mg quartz groups.